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Ornithine Technical Reports

Ornithine is an amino acid that works to prevent cancer and improve the immune system.  Here are a group of medical studies which describe this role for Ornithine.

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HealthGate Documents

Record 1 from database: MEDLINE
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Title

Transport of thyroid hormones to target tissues.

Author

Ekins RP; Sinha AK; Pickard MR; Evans IM; al Yatama F

Address

Division of Molecular Endocrinology, University College London Medical School, United Kingdom.

Source

Acta Med Austriaca, 1994, 21:2, 26-34

Abstract

Endemic iodine deficiency is associated with maternal hypothyroxinemia and a relatively high incidence of neurological disorders in the offspring. The previous assumption that the placenta is impermeable to maternal thyroid hormone, has resulted in the erroneous suggestion that iodine per se has an essential role in brain development. Furthermore, the observed factorial rise in thyroxine-binding globulin (TBG) in pregnancy has often been misinterpreted as preventing thyroid hormone loss to either the fetal compartment or excretory systems. However, physiochemical analysis of the role of specific binding proteins in hormone delivery, combined with epidemiological evidence and evolutionary considerations has led us to postulate that a) maternal thyroxine (T4) is transported to the fetus, and is of crucial importance in early fetal development, and b) TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Placental transfer of maternal T4 in a variety of mammalian species (including humans) is now well established. Further experimental studies in rats have shown that perturbation of the intrauterine thyroid hormone environment during critical phases of brain development results in a spectrum of biochemical dysgenesis. For example, in fetal brains deriving from hypothyroxinemic (Tx) rat dams, severe disruption of phosphate metabolism is observed and the ontogenesis of two enzyme activities associated with growth control, protein kinase C and ornithine decarboxylase, are compromised. Development of brain function is also impaired, as evidenced by the dysgenesis of certain neurotransmitter metabolic activities (choline acetyltransferase and DOPA decarboxylase).(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

95091118

MeSH Heading (Major)

Fetal Development|*PH; Goiter, Endemic|*PP; Maternal-Fetal Exchange|*PH; Thyroid Hormones|*BL

MeSH Heading

Animal; Brain|EM; Carrier Proteins|PH; Female; Fetal Organ Maturity|PH; Human; Infant, Newborn; Membrane Proteins|PH; Pregnancy; Rats; Support, Non-U.S. Gov't; Thyroid Gland|EM; Thyroxine|BL; Thyroxine-Binding Proteins|PH

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0303-8173

Country of Publication

AUSTRIA

Record 2 from database: MEDLINE
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Title

Biochemical and growth-modulatory effects of the new S-adenosylmethionine decarboxylase inhibitor CGP 48664 in malignant and immortalized normal human breast epithelial cells in culture.

Author

Manni A; Badger B; Wechter R; Kunselman S; Rossini A; Demers L

Address

Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.

Source

Int J Cancer, 1995 Aug, 62:4, 485-91

Abstract

CGP 48664 [4-aminoindanon-1-(2'-amidino)hydrazone dihydrochloride monohydrate] is a newly introduced inhibitor of S-adenosylmethionine decarboxylase (SAMDC) with increased selectivity of action and reduced toxicity. We analyzed the biochemical and antiproliferative effects of this compound in a panel of hormone-dependent (3 clones of MCF-7, T47D) and -independent (MDA-MB-231, BT-20) human breast cancer cell lines in culture. For comparison, we also tested its effects in the spontaneously immortalized human breast epithelial cell line MCF-10A. All cell lines were highly sensitive to the growth-inhibitor effect of CGP 48664 with an IC50 between 0.1 and 0.5 microM. A dose-dependent bell-shaped increase in SAMDC was observed in normal and malignant breast cells resulting from enzyme stabilization by the inhibitor as supported by Western blot analysis. While ornithine decarboxylase (ODC) activity consistently increased, the effect of CGP 48664 on spermidine/spermine N'acetyltransferase (SSAT) was variable in the breast cancer cell lines. In contrast, the inhibitor consistently reduced SSAT activity level in the MCF-10A cell line and its derivative partially transformed by a mutated ras oncogene. As expected cellular putrescine levels were markedly increased by CGP 48664 administration, whereas spermidine and spermine contents were reduced. However, the degree of reduction was usually only moderate. Furthermore, exogenous polyamine administration was relatively ineffective in rescuing the antiproliferative effect of CGP 48664 in MCF-7 cells, while exerting a more complete rescue in the MDA-MB-231 cell line. We conclude that CGP 48664 exerts a potent growth-inhibitory effect on mammary cells in culture. However, its action may not always be entirely mediated through the polyamine pathway.

Language of Publication

English

Unique Identifier

95362369

MeSH Heading (Major)

Acetyltransferases|*ME; Adenosylmethionine Decarboxylase|*AI; Amidines|*PD; Breast|*DE/EN/PA; Breast Neoplasms|*DT/EN/PA; Indans|*PD; Ornithine Decarboxylase|*ME

MeSH Heading

Cell Division|DE; Cell Line, Transformed; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Human; Neoplasms, Hormone-Dependent|DT; Spermidine|ME/PD; Spermine|PD; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0020-7136

Country of Publication

UNITED STATES

Record 3 from database: MEDLINE
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Title

Structure-activity relations of S-adenosylmethionine decarboxylase inhibitors on the growth of MCF-7 breast cancer cells.

Author

Thomas T; Faaland CA; Adhikarakunnathu S; Thomas TJ

Address

Department of Environmental & Community Medicine, Environmental and Occupational Health Sciences Institute, New Brunswick, NJ, USA.

Source

Breast Cancer Res Treat, 1996, 39:3, 293-306

Abstract

SAMDC is a key enzyme in the biosynthesis of spermidine and spermine, 2 polyamines that are essential for cell proliferation. Inhibition of polyamine biosynthesis is often targeted as a therapeutic strategy to suppress cancer cell growth as these cells contain elevated levels of polyamines. We examined the effect of a new group of SAMDC inhibitors, CGP33829, CGP35753, CGP36958, CGP39937, and CGP48664, (obtained from Ciba-Geigy, Basel, Switzerland), and their parent compound, MGBG, on the proliferation of MCF-7 breast cancer cells. MGBG had minimal effects on the proliferation of MCF-7 cells up to 6 microM concentration. In contrast, CGP48664 and CGP39937, containing 2 aromatic rings that delocalize the pi electron system of the backbone of MGBG, were potent inhibitors with 50% growth inhibition at 0.5 microM concentration. Other CGP compounds were less effective in inhibiting cell growth. The ability of CGP48664 to inhibit MCF-7 cell proliferation was related to its ability to inhibit SAMDC and to consequently deplete spermidine and spermine levels in the cell. Exogenous spermidine and spermine could reverse the growth inhibitory effects of this compound. CGP compounds also increased the activity of ODC, another enzyme involved in polyamine biosynthesis. Northern blot analysis of mRNA from MCF-7 cells progressing in cell cycle after G1 synchronization did not show an increase in ODC mRNA level by CGP48664. These data demonstrate structure-activity relationships of a series of MGBG derivatives on cell growth, enzyme activities, and polyamine biosynthesis in a hormone-responsive breast cancer cell line and suggest potential application of SAMDC inhibitors as therapeutic agents.

Language of Publication

English

Unique Identifier

97031083

MeSH Heading (Major)

Adenosylmethionine Decarboxylase|*AI/GE; Antineoplastic Agents|*PD; Breast Neoplasms|*DT/PA; Enzyme Inhibitors|*PD

MeSH Heading

Acetyltransferases|ME; Amidines|PD; Biogenic Polyamines|AN; Cell Division|DE; Estradiol|PD; Female; Human; Indans|PD; Mitoguazone|PD; Ornithine Decarboxylase|ME; RNA, Messenger|AN; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

Record 4 from database: MEDLINE
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Title

Polyamine profiles and growth properties of ornithine decarboxylase overexpressing MCF-7 breast cancer cells in culture.

Author

Manni A; Wechter R; Grove R; Wei L; Martel J; Demers L

Address

Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.

Source

Breast Cancer Res Treat, 1995 Apr, 34:1, 45-53

Abstract

To determine the direct influence of the polyamine (PA) pathway on breast cancer phenotype, we employed a transfection approach to induce overexpression of the PA biosynthetic enzyme ornithine decarboxylase (ODC) in the hormone-responsive MCF-7 breast cancer cell line. Using a modified calcium phosphate method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient transfection system. ODC-overexpressing MCF-7 cells exhibited a selective increase in cellular putrescine content, while the levels of spermidine and spermine remained unaffected. Under defined culture conditions, overexpression of ODC resulted in a consistent but modest increase in [3H]thymidine incorporation into DNA which was similar in the presence and absence of 17-beta-estradiol, TGF-alpha, and IGF-I. In the presence of serum, the effect of ODC overexpression on basal [3H]-thymidine incorporation into DNA was inconsistent, possibly as a result of subtle differences in culture conditions. Overall, our results support the hypothesis that activation of the PA biosynthetic pathway may confer a growth advantage to breast cancer cells.

Language of Publication

English

Unique Identifier

95268110

MeSH Heading (Major)

Breast Neoplasms|*EN/GE/PA; Ornithine Decarboxylase|GE/*ME

MeSH Heading

Cell Division; Female; Gene Expression Regulation, Enzymologic; Human; Polyamines|ME; Support, U.S. Gov't, P.H.S.; Transfection; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

Record 5 from database: MEDLINE
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Title

Prevention of breast cancer in premenopausal women.

Author

Love RR

Address

University of Wisconsin Comprehensive Cancer Center, Department of Human Oncology, Madison 53706.

Source

J Natl Cancer Inst Monogr, 1994, :16, 61-5

Abstract

While all-inclusive complete models for breast cancer development are not available, four concepts are likely to be critical to creation of well-grounded breast cancer prevention efforts: 1) step-by-step progressive development, 2) involving multiple factors, 3) over several years, and 4) during a long period of which the process may be reversible. Interventions to prevent breast cancer must have a comprehensive biological rationale, an absence of serious toxic effects, and long-term acceptability by women. Prophylactic mastectomy may be beneficial in some women, but identification of individuals at very high risk for breast cancer remains elusive. At present, greater attention to four manipulable risk factors is appropriate: radiation, smoking, alcohol, and lactation. Clinical trials are in the process of studying a synthetic retinoid (4-hydroxyphenylretinamide), tamoxifen, and a low-fat diet. Other breast cancer prevention strategies in various phases of preclinical trial evaluation include: pseudopregnancy, an "ideal" combination oral contraceptive, luteinizing hormone-releasing hormone (LHRH) agonist oophorectomy, modification of estrogen metabolism, suppression of ornithine decarboxylase induction, and manipulation of growth factors.

Language of Publication

English

Unique Identifier

95092435

MeSH Heading (Major)

Breast Neoplasms|EP/ET/*PC

MeSH Heading

Adult; Ataxia Telangiectasia|CO; Cocarcinogenesis; Contraceptives, Oral, Hormonal|AE/TU; Dietary Fats|AD/AE; Estrogens|ME; Female; Fenretinide|PD; Gonadorelin|AG; Human; Lactation; Mastectomy; Neoplasms, Radiation-Induced|PC; Ornithine Decarboxylase|AI; Premenopause; Prospective Studies; Pseudopregnancy|CI; Randomized Controlled Trials; Risk Factors; Smoking; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tamoxifen|TU; Temperance; Time Factors

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1052-6773

Country of Publication

UNITED STATES

Record 6 from database: MEDLINE
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Title

Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines.

Author

Mehta K; Pantazis P; McQueen T; Aggarwal BB

Address

Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.

Source

Anticancer Drugs, 1997 Jun, 8:5, 470-81

Abstract

Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a major active component of the food flavor turmeric (Curcuma longa) that exhibits anticarcinogenic properties in vivo. In vitro, it suppressed c-jun/Ap-1 and NF-kappaB activation and type 1 human immunodeficiency virus long-terminal repeat-directed gene expression. We examined the antiproliferative effects of curcumin against several breast tumor cell lines, including hormone-dependent and -independent and multidrug-resistant (MDR) lines. Cell growth inhibition was monitored by [3H]thymidine incorporation, Trypan blue exclusion, crystal violet dye uptake and flow cytometry. All the cell lines tested, including the MDR-positive ones, were highly sensitive to curcumin. The growth inhibitory effect of curcumin was time- and dose-dependent, and correlated with its inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested cells in the G2/S phase of the cell cycle. Curcumin-induced cell death was neither due to apoptosis nor to any significant change in the expression of apoptosis-related genes, including Bcl-2, p53, cyclin B and transglutaminase. Overall our results suggest that curcumin is a potent antiproliferative agent for breast tumor cells and may have potential as an anticancer agent.

Language of Publication

English

Unique Identifier

97358515

MeSH Heading (Major)

Antineoplastic Agents|*PD; Breast Neoplasms|*PA; Curcumin|*PD

MeSH Heading

Antibiotics, Anthracycline|PD; Blotting, Western; Cell Cycle|DE; Cell Division|DE; Cell Line; Doxorubicin|PD; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Human; Ornithine Decarboxylase|ME; Support, Non-U.S. Gov't; Tetrazolium Salts; Thiazoles

Publication Type

JOURNAL ARTICLE

ISSN

0959-4973

Country of Publication

ENGLAND

Record 7 from database: MEDLINE
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Title

Can arginine and ornithine support gut functions?

Author

Cynober L

Address

Laboratoire de Biochimie, HÈopital Saint-Antoine, Paris, France.

Source

Gut, 1994 Jan, 35:1 Suppl, S42-5

Abstract

Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported. One recent animal study showed improved morphology after OKG administration, perhaps through increased polyamine secretion. Generation of nitric oxide from arginine has two facets. Excess production from high dose arginine potentiated the effects of experimentally induced sepsis, whereas low doses improved survival. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.

Language of Publication

English

Unique Identifier

94171129

MeSH Heading (Major)

Arginine|*ME/PD; Enteral Nutrition|*; Intestines|DE/ME/*PH; Ornithine|*ME/PD

MeSH Heading

Citrulline|ME; Human; Nitric Oxide|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0017-5749

Country of Publication

ENGLAND

Record 8 from database: MEDLINE
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Title

Chlorpheniramine inhibits the synthesis of ornithine decarboxylase and the proliferation of human breast cancer cell lines [published erratum appears in Breast Cancer Res Treat 1996;37(1):97]

Author

Medina MA; García de Veas R; Morata P; Lozano J; Sánchez Jiménez F

Address

Laboratorio de BioquÆimica y BiologÆia Molecular, Facultad de Ciencias, Universidad de MÆalaga, Spain.

Source

Breast Cancer Res Treat, 1995 Aug, 35:2, 187-94

Abstract

Proliferation of both mouse and human breast cancer cells was inhibited by chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential phase of growth (two days after seeding), 250 microM CPA was able to reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). The antiproliferative effect of CPA was also tested on a poorly-differentiated and hormone-insensitive human breast cancer cell line (MDA-MB231) and on a highly proliferative human colon cancer cell line (clone 3). CPA was cytotoxic for MDA-MB231 cells at concentrations higher than 50 microM, and it was also cytotoxic for the colon cancer cell clone 3 at 250 microM CPA. Nevertheless, colon cancer cells were slightly stimulated at CPA concentrations less than 100 microM. CPA reduced (by 50-70%) the ornithine decarboxylase induction occurring early after culture seeding of experimental mammary tumors (Ehrlich carcinoma cells) and human breast cancer cells (MCF-7). The presented data suggest that in addition to ODC inhibition, CPA presents other still unknown cytotoxic effects.

Language of Publication

English

Unique Identifier

95375276

MeSH Heading (Major)

Breast Neoplasms|*EN/PA; Chlorpheniramine|*PD; Ornithine Decarboxylase|*BI/GE

MeSH Heading

Animal; Cell Division|DE; Colonic Neoplasms|EN/GE/PA; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic|DE; Human; Mammary Neoplasms, Experimental|EN/GE/PA; Mice; RNA, Messenger|GE; Support, Non-U.S. Gov't; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

Record 9 from database: MEDLINE
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Title

Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and pituitary factors.

Author

Shiu RP; Lima G; Leung CK; Dembinski TC

Address

 

Source

J Steroid Biochem, 1986 Jan, 24:1, 133-8

Abstract

Although polyamines are important in regulating proliferation of mammalian cells, their role in hormone induction of cell growth has not been delineated. In the estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M) was able to stimulate cell proliferation and the activity of

decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine, the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO abolished the estradiol-induced growth of several other estrogen-responsive human breast cancer cell lines but did not affect the growth of hormone-independent cell lines. Further, a serum factor was found to be required for estradiol to exert its effect. To gain insight into the nature of this and possibly other extrinsic factors involved, the effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a different site dramatically potentiated the effect of estradiol on the growth of the breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other estrogen receptor-positive human breast cancer cell lines in vitro under serum-free condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are importance for estrogen to exert its mitogenic action. The next goal will be to elucidate the mechanisms of action of these molecules in the modulation of estrogen action.

Language of Publication

English

Unique Identifier

86201682

MeSH Heading (Major)

Breast Neoplasms|*PA; Estrogens|*PD; Pituitary Gland|*PH; Polyamines|*ME

MeSH Heading

Animal; Cell Line; Drug Synergism; Female; Human; Mice; Mice, Nude; Neoplasm Transplantation; Ornithine|AA/PD; Ornithine Decarboxylase|AN; Pituitary Neoplasms|SE; Support, Non-U.S. Gov't; Transplantation, Heterologous

Publication Type

JOURNAL ARTICLE

ISSN

0022-4731

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Estrogens); 0 (Polyamines); 70052-12-9 (Eflornithine); 7006-33-9 (Ornithine)

Record 10 from database: MEDLINE
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Title

Ornithine alpha-ketoglutarate in nutritional support.

Author

Cynober L

Address

Laboratoire de Biochimie, Hopital Saint Antoine, Paris, France.

Source

Nutrition, 1991 Sep-Oct, 7:5, 313-22

Abstract

Ornithine alpha-ketoglutarate (OKG) is a salt formed of two molecules of ornithine and one molecule of alpha-ketoglutarate. OKG has been successfully used by the enteral and parenteral route in burn, traumatized, and surgical patients and in chronically malnourished subjects. According to the metabolic situation, OKG treatment decreases muscle protein catabolism and/or increases synthesis. In addition, OKG promotes wound healing. The mechanism of action of OKG is not fully understood, but the secretion of anabolic hormones (insulin, human growth hormone) and the synthesis of metabolites (glutamine, polyamines, arginine, ketoacids) may be involved.

Language of Publication

English

Unique Identifier

92208515

MeSH Heading (Major)

Nutrition|*; Ornithine|*AA/AD/AE/CH/ME/PK/TU

MeSH Heading

Animal; Chemistry, Physical; Enteral Nutrition; Human; Nutrition Disorders|TH; Parenteral Nutrition; Wound Healing

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0899-9007

Country of Publication

UNITED STATES

CAS Registry/EC Number

37339-58-5 (ornicetil); 7006-33-9 (Ornithine)

Record 11 from database: MEDLINE
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Title

Role of ornithine decarboxylase in proliferation of prolactin-dependent lymphoma cells.

Author

Elsholtz HP; Shiu RP; Friesen HG

Address

 

Source

Biochem Cell Biol, 1986 May, 64:5, 381-6

Abstract

Mitogenic stimulation of Nb2 lymphoma cells by lactogenic hormones (prolactin, human growth hormone) caused a dramatic early increase in ornithine decarboxylase (ODC) activity that achieved a maximal level by 6-8 h. A marked increase in ODC activity was also generated when cells which had reached a growth plateau were transferred to fresh medium that did not stimulate growth. Furthermore, low concentrations of human growth hormone (20 pg/mL) elicited a proliferative response, but did not cause a detectable early increase in ODC activity. The early peak of ODC activity thus appeared not to be directly involved in mediating lactogen-stimulated growth nor was it required to support the mitogenic response. However, prolonged suppression of ODC activity by DL-alpha-difluoromethylornithine (DFMO) (200 microM) attenuated the growth of Nb2 cells (50-60% inhibition), indicating that normal cell growth was dependent on ODC and polyamine biosynthesis. Under these conditions, putrescine, the enzyme product, or the polyamines spermidine and spermine restored normal cell growth when added at a concentration of 1 microM or greater. Nb2-SP cells, variants which proliferate in the absence of prolactin, were about two times more resistant to the growth suppressive effects of DFMO than prolactin-responsive Nb2 cells.

Language of Publication

English

Unique Identifier

86242765

MeSH Heading (Major)

Lymphoma|EN/*PA; Ornithine Decarboxylase|AI/*ME; Prolactin|*PD; Somatotropin|*PD

MeSH Heading

Animal; Cell Division|DE; Cell Line; Human; Kinetics; Ornithine|AA/PD; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0829-8211

Country of Publication

CANADA

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 70052-12-9 (Eflornithine); 7006-33-9 (Ornithine); 9002-62-4 (Prolactin); 9002-72-6 (Somatotropin)

Record 12 from database: MEDLINE
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Title

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Author

Izdebski J; Pinski J; Horvath JE; Halmos G; Groot K; Schally AV

Address

Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70146, USA.

Source

Proc Natl Acad Sci U S A, 1995 May, 92:11, 4872-6

Abstract

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Language of Publication

English

Unique Identifier

95281558

MeSH Heading (Major)

Oligopeptides|CS/*PD; Pituitary Gland|DE/*SE; Somatotropin|BL/*SE; Somatotropin-Releasing Hormone|*AA/AG/*CS/PD

MeSH Heading

Amino Acid Sequence; Animal; Comparative Study; Human; In Vitro; Male; Molecular Sequence Data; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide|ME; Receptors, Pituitary Hormone-Regulating Hormone|ME; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
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Title

Effects of parathyroid hormone-related peptide on adenosine 3',5'-monophosphate and ornithine decarboxylase in a human colonic cell line.

Author

Yu D; Seitz PK; Selvanayagam P; Rajaraman S; Townsend CM Jr; Cooper CW

Address

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.

Source

Endocrinology, 1992 Apr, 130:4, 1993-2000

Abstract

PTH-related peptide (PTHrP) is widely distributed in normal tissues, including the gut, and is considered a potential autocrine or paracrine regulator of cellular growth and differentiation. With this in mind, a human colonic cell line (LoVo) was used to study the effect of PTHrP on ornithine decarboxylase (ODC), because ODC is known to have profound effects on the growth and differentiation of many cell types via stimulation of synthesis of polyamines. cAMP also was measured, because this second messenger has been implicated in the regulation of ODC activity. Nearly confluent LoVo cells, grown in F-12 medium and 10% fetal bovine serum (FBS), were preincubated in 1% FBS for at least 5 h, and then PTHrP-(1-34) was added, and the incubation was continued for up to 6 h. Cell extracts were analyzed for ODC activity by measuring 14CO2 liberated from 14C-labeled ornithine, for cAMP by RIA, and for ODC mRNA by Northern analysis. PTHrP produced dose-related increases in both cAMP (2- to 3-fold) and ODC (3- to 5-fold), with a maximal effect at 0.1-1 microM and an ED50 of 1-10 nM. Comparison of the cAMP and ODC responses to PTHrP showed a strong correlation (r = 0.96; P less than 0.001). The effects of 1 microM PTHrP-(1-34) to increase cAMP and ODC were completely inhibited by 10-20 microM of the specific antagonist [Asn10,Leu11]PTHrP-(7-34). PTHrP-(1-34) did not stimulate ODC activity when cells were incubated without FBS. The stimulation of ODC activity by PTHrP-(1-34) was maximal at 2 h, a time at which an increase in ODC mRNA also was evident. PTH-(1-34) and forskolin also stimulated ODC activity, but PTHrP-(67-86) amide was ineffective. The results indicate that the N-terminal portion of the PTHrP molecule can stimulate ODC activity in a human colon cell line and that the effect is probably mediated by cAMP. The results are consistent with the idea that PTHrP may influence cell growth and differentiation in the gut via an effect on polyamine biosynthesis. Since LoVo cells also express PTHrP mRNA, this gastrointestinal cell line may serve as a useful model for studying autocrine regulation of gut cell growth and differentiation by PTHrP.

Language of Publication

English

Unique Identifier

92191895

MeSH Heading (Major)

Colon|CH/*DE; Cyclic AMP|*AN; Ornithine Decarboxylase|*AN/GE; Parathyroid Hormones|*PD; Proteins|GE/*PD

MeSH Heading

Cell Line; Human; Peptide Fragments|PD; RNA, Messenger|AN; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0013-7227

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (parathyroid hormone-related protein); 0 (Parathyroid Hormones); 0 (Peptide Fragments); 0 (Proteins); 0 (RNA, Messenger); 112540-82-6 (hypercalcemic hormone of malignancy (1-34)); 52232-67-4 (Teriparatide); 60-92-4 (Cyclic AMP)

Record 14 from database: MEDLINE
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Title

Effects of vasoactive intestinal peptide on adenosine 3',5'-monophosphate, ornithine decarboxylase, and cell growth in a human colon cell line.

Author

Yu D; Seitz PK; Selvanayagam P; Rajaraman S; Townsend CM Jr; Cooper CW

Address

Department of Pharmacology, University of Texas Medical Branch, Galveston 77550.

Source

Endocrinology, 1992 Sep, 131:3, 1188-94

Abstract

Vasoactive intestinal peptide (VIP) is a widely distributed neuropeptide that has been considered a potential regulator of cell growth and differentiation in various tissues, including the gut. To examine this idea, we used a human colon carcinoma cell line (LoVo) as a model system and measured ornithine decarboxylase (ODC), because this is the rate-limiting enzyme for the formation of polyamines, which are thought to be key factors in regulating cell growth. LoVo cells, grown to about 80% confluence in F-12 medium containing 10% fetal bovine serum, were preincubated for 5 h in low serum medium (1% fetal bovine serum in F-12), and ODC activity was determined by measuring 14CO2 liberated from 14C-labeled ornithine. VIP caused a dose-related biphasic change in ODC, with activity increased at 10 pM, maximal (5-fold increase) at 10 nM, and decreased toward basal at 100 nM to 1 microM. Incubation of cells for 6 days with VIP in low serum medium showed similar changes in cell numbers, with growth being increased by doses in the 1 pM to 100 nM range and decreased at higher doses (greater than or equal to 100 nM). Exposure of cells to 5 mM alpha-difluoromethylornithine blocked both the VIP-induced increase in cell number and the VIP-induced increase in ODC activity. Increased ODC mRNA was detected after 2 h of exposure to VIP, a time at which ODC activity peaked after treatment, and the increase in ODC mRNA caused by VIP was dose-dependent. In related experiments LoVo cells were found to have high affinity VIP receptors (Kd = 0.4 nM), as assessed by examination of [125I]VIP binding in the presence of varying concentrations of unlabeled VIP. Studies of intracellular cAMP revealed a dose-related increase in cAMP in response to VIP (ED50 = 11 pM), and the adenylate cyclase activator forskolin increased both ODC activity and ODC mRNA. The findings support the idea that LoVo cells have VIP receptors linked to cAMP which can stimulate cell growth at least in part by increasing ODC synthesis and activity, thereby altering the production of polyamines. The decreased growth and ODC activity observed with high doses of VIP may involve a second messenger other than cAMP.

Language of Publication

English

Unique Identifier

92371314

MeSH Heading (Major)

Cell Division|*DE; Cyclic AMP|*ME; Ornithine Decarboxylase|GE/*ME; Vasoactive Intestinal Peptide|ME/*PD

MeSH Heading

Adenocarcinoma; Blotting, Northern; Cell Line; Colonic Neoplasms; Dose-Response Relationship, Drug; Eflornithine|PD; Human; Kinetics; Receptors, Gastrointestinal Hormone|ME; RNA, Messenger|ME; RNA, Neoplasm|GE/IP; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0013-7227

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Gastrointestinal Hormone); 0 (Receptors, Vasoactive Intestinal Peptide); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 37221-79-7 (Vasoactive Intestinal Peptide); 60-92-4 (Cyclic AMP); 70052-12-9 (Eflornithine)

Record 15 from database: MEDLINE
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Title

Characterization and growth factor stimulation of L-arginine transport in a human colon cancer cell line.

Author

Cendan JC; Souba WW; Copeland EM 3rd; Lind DS

Address

Department of General Surgery, University of Florida College of Medicine, Gainesville 32610, USA.

Source

Ann Surg Oncol, 1995 May, 2:3, 257-65

Abstract

BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are potent mitogens that contribute to abnormal growth regulation in colon cancer. Growth factors have been shown to regulate transmembrane nutrient uptake as an adaptive response to support cellular proliferation. METHODS: The transport of L-arginine by the SW480 primary human colon adenocarcinoma cell line was characterized by assaying the uptake of [3H]L-arginine in the presence and absence of sodium. Kinetic studies were performed over a range of L-arginine concentrations to determine transport affinity (Km) and maximal transport velocity (Vmax). To further characterize the specific transporters, [3H]L-arginine uptake was measured in the presence of selected amino acids, hormones, and under conditions of varying external pH. To investigate the effects of EGF and TGF alpha, cells were incubated with increasing doses of growth factors (1, 10, 50 ng/ml) and L-arginine transport was measured at various time intervals (8, 12, 24 h). Proliferation was assessed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 3 days after growth factor stimulation. RESULTS: The majority of carrier-mediated L-arginine transport was via a sodium-independent process (65-70%), whereas the remainder was sodium-dependent (28-30%). Diffusion contributed a small amount to total L-arginine uptake (2%). Kinetic studies of arginine transport revealed a single high-affinity Na(+)-independent transporter with a Km = 55.8 +/- 5.8 microM and a Vmax = 710.6 +/- 87.3 pM/mg protein/30 s. Na(+)-independent arginine uptake was pH-insensitive and markedly inhibited by system y+ substrates L-homoarginine, L-lysine, and L-ornithine. A single Na(+)-dependent transporter with a Km = 19.8 +/- 2.3 microM and a Vmax = 159.1 +/- 8.9 pM/mg protein/30 s was identified. Na(+)-dependent arginine uptake was inhibited by system BO,+ substrates L-lysine, L-ornithine, L-leucine, L-cysteine, and L-glutamine, but not by 2-methylaminoisobutyric acid. In addition, Na(+)-dependent arginine uptake was pH- and hormone-insensitive. Incubation with EGF or TGF alpha had no effect on Na(+)-independent L-arginine uptake; however, Na(+)-dependent uptake was enhanced 60% by EGF (10 ng/ml, p < 0.05) and 100% by TGF alpha (10 ng/ml, p < 0.05), whereas cellular proliferation was increased 27% by EGF (10 ng/ml, p < 0.05) and 37% by TGF alpha (10 ng/ml, p < 0.01). CONCLUSIONS: L-arginine transport in the SW480 colon cancer cell line is principally mediated by the Na(+)-independent system y+ and to a lesser extent by the Na(+)-dependent system BO,+. Furthermore, EGF and TGF alpha preferentially stimulate L-arginine uptake via the Na(+)-dependent transporter, ostensibly to accommodate for the mitogenic stimulus.

Language of Publication

English

Unique Identifier

95368445

MeSH Heading (Major)

Adenocarcinoma|*ME; Arginine|*PK; Colonic Neoplasms|*ME; Epidermal Growth Factor-Urogastrone|CH/*PD; Transforming Growth Factor alpha|CH/*PD

MeSH Heading

Amino Acids|PD; Carrier Proteins; Cell Division|DE; Cell Membrane Permeability|DE; Human; Hydrogen-Ion Concentration; Ion Channel Gating|DE; Nitric Oxide|BI; Radioisotopes; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells, Cultured|ME

Publication Type

JOURNAL ARTICLE

ISSN

1068-9265

Country of Publication

UNITED STATES

Record 16 from database: MEDLINE
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Title

Epidermal growth factor labeled beta-amanitin-poly-L-ornithine: preparation and evidence for specific cytotoxicity.

Author

Bermbach U; Faulstich H

Address

Max-Planck-Institut für medizinische Forschung, Abteilung Physiologie, Heidelberg, West Germany.

Source

Biochemistry, 1990 Jul 24, 29:29, 6839-45

Abstract

Poly-L-ornithine with an average molecular weight of 32K was reacted with beta-amanitin hydroxysuccinimide ester to form an amide-linked toxin conjugate. Loading of the polymeric chain with amanitin was high, corresponding to up to 35% of the total weight. To this amatoxin vehicle we attached a targeting molecule, human recombinant leucine-21 epidermal growth factor (hrEGFL), via a disulfide-containing linker moiety. A typical average stoichiometry of the hrEGFL labeled toxin conjugate was (L-Orn)164(beta-amanitin)19(COC2H4SSC2H4CO-hrEGFL)2. The affinity for EGF receptors of hrEGFL bound in this conjugate was tested by using A 431 cells. The affinity was eight times lower than that of unsubstituted hrEGFL but regarded as high enough for studying specific toxicity effects with cells bearing EGF receptors. We found that beta-amanitin in the labeled conjugate was able to inhibit the growth of A 431 cells at a concentration of 28 nM, 80 times lower than for native beta-amanitin and 20 times lower than for poly-L-ornithine-bound beta-amanitin without the hrEGFL label. The approximately 20-fold enhancement of cytotoxicity suggests a specific internalization of the toxin conjugate mediated by the hormone label. This idea is supported by the fact that also in another transformed fibroblast cell line, with an increased though smaller number of EGF receptors than A 431 cells, the corresponding enhancement of cytotoxicity was demonstrable but less pronounced (7-fold). The hormone-mediated increase in cytotoxicity of EGF labeled poly-L-ornithine-beta-amanitin conjugates, combined with their moderate toxicity in the mouse, encourages further examination of such compounds in tumor model systems in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

90373797

MeSH Heading (Major)

Amanitins|*/TO; Epidermal Growth Factor-Urogastrone|*/ME; Peptides|*

MeSH Heading

Animal; Cytotoxins; Human; Receptors, Epidermal Growth Factor-Urogastrone|ME; Support, Non-U.S. Gov't; Tumor Cells, Cultured|DE/ME

Publication Type

JOURNAL ARTICLE

ISSN

0006-2960

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amanitins); 0 (Cytotoxins); 0 (Peptides); 0 (Receptors, Epidermal Growth Factor-Urogastrone); 21150-22-1 (beta-amanitin); 25104-12-5 (polyornithine); 62229-50-9 (Epidermal Growth Factor-Urogastrone)

Record 17 from database: MEDLINE
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Title

Role of polyamines in the growth of hormone-responsive and -resistant human breast cancer cells in nude mice.

Author

Manni A; Badger B; Martel J; Demers L

Address

Department of Medicine, Pennsylvania State University, Hershey 17033.

Source

Cancer Lett, 1992 Sep 14, 66:1, 1-9

Abstract

Recent in vitro data suggest that at least some hormone-independent breast cancer cells exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To address this issue under conditions of in vivo growth, we tested the antiproliferative effect of the polyamine synthetic inhibitor alpha-difluoromethyl-ornithine (DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth of established tumors to a similar extent in all cell lines, even though tumor regression was only observed with MCF-7 cells. DFMO, while inhibiting E2-supported MCF-7 breast cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines, while the spermine level was unaffected. Cellular putrescine levels were suppressed in MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7 or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors develop in some mice upon discontinuation of the drug. We conclude that the hormone-independent breast cancer cell lines tested do not exhibit increased polyamine biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice.

Language of Publication

English

Unique Identifier

93082651

MeSH Heading (Major)

Breast Neoplasms|DT/*PA/PP; Neoplasms, Hormone-Dependent|DT/*PA/PP; Polyamines|*

MeSH Heading

Animal; Cell Division|DE; Comparative Study; Drug Resistance; Drug Screening Assays, Antitumor; Eflornithine|PD; Human; Mice; Mice, Nude; Neoplasm Transplantation; Putrescine|ME/PH; Spermidine|ME/PH; Spermine|ME/PH; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured|DE

Publication Type

JOURNAL ARTICLE

ISSN

0304-3835

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Polyamines); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 70052-12-9 (Eflornithine); 71-44-3 (Spermine)

Record 18 from database: MEDLINE
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Title

Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study.

Author

Carel JC; Tresca JP; Letrait M; Chaussain JL; Lebouc Y; Job JC; Coste J

Address

Association France Hypophyse, HÈopital Cochin, Paris, France. jccarel@infobiogen.fr

Source

J Clin Endocrinol Metab, 1997 Jul, 82:7, 2117-21

Abstract

Evaluation of GH secretion using pharmacological GH stimulation tests (GHST) remains a current practice, although the reliability of GHST has been questioned, and many pitfalls have been pointed out. We have analyzed all of the 6373 GH stimulation tests that led to the initiation of GH therapy in 3233 children treated in France from 1973-1989. Tests and GH measurements were performed by individual centers and collected by the Association France-Hypophyse. GH deficiency (GHD) was due to craniospinal irradiation (11%), was due to organic causes or associated with multiple deficiencies (22%), or was considered idiopathic (65%); 2% of the patients were considered non-GHD. Eleven different pharmacological tests were used, and 62 of the 66 theoretical pairs of tests were used at least once. The most frequent combination of tests (ornithine in one instance and insulin in another) was used in 12.7% of patients. The reliability of the GH peak measured by comparing the results of 2 tests in the same patient was poor, as measured by intraclass correlation coefficients below 0.8. Multivariate analysis identified several parameters positively or negatively associated with peak plasma GH: calendar year of initiation of treatment, etiology of GHD, height SD score, bone age SD score, puberty, weight SD score, genetic target height SD score, and the nature of the pharmacological agent used. We believe that several of these factors (weight SD score, genetic target height SD score, and nature of the agent) identify biases in the diagnosis of GHD. We conclude that GHST should be performed with a very limited number of agents, interpreted after the establishment of reference values in age-matched normal children, and associated with other clinical and biochemical parameters for establishing the diagnosis of GHD.

Language of Publication

English

Unique Identifier

97358161

MeSH Heading (Major)

Somatotropin|*BL/*DF

MeSH Heading

Adolescence; Age Factors; Child; Child, Preschool; Female; Human; Male; Methods; Registries; Reproducibility of Results; Retrospective Studies

Publication Type

JOURNAL ARTICLE

ISSN

0021-972X

Country of Publication

UNITED STATES

Record 19 from database: MEDLINE
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Title

Insulin induction of ornithine decarboxylase. Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E.

Author

Manzella JM; Rychlik W; Rhoads RE; Hershey JW; Blackshear PJ

Address

Howard Hughes Medical Institute Laboratories, Duke University Medical Center, Durham, North Carolina 27710.

Source

J Biol Chem, 1991 Feb 5, 266:4, 2383-9

Abstract

We investigated the possibility that insulin could stimulate translation of ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line that expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h after exposure to 70 nM insulin, ODC enzyme activity increased approximately 50-fold and mRNA accumulation 3-fold in the HIR 3.5 cells but not in normal fibroblasts. Pretreatment of cells with cycloheximide completely inhibited insulin-stimulated ODC expression; actinomycin D partially inhibited this effect. To determine the influence of the 5' untranslated region (5'UTR) of ODC mRNA on insulin-regulated ODC expression, plasmids were constructed which contained sequences from the 5'UTR of a rat ODC mRNA interposed between the ferritin promoter and the coding region of the human growth hormone gene. These constructions were then expressed transiently in HIR 3.5 cells. Insulin stimulated a 2-4-fold change in growth hormone accumulation in the medium of cells transiently expressing plasmids containing the entire 5'UTR of ODC mRNA or just the 5'-most 115 bases, a G/C-rich conserved sequence predicted to form a stem-loop structure and shown previously to be responsible for constitutive inhibition of translation. There was a direct correlation between the extent of insulin stimulation and the predicted secondary structure of the added 5'UTR sequences. To determine whether this effect might be due to insulin activation of initiation factors responsible for melting mRNA secondary structure, we examined the effect of insulin on the phosphorylation states of two such factors, eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the phosphorylation of both initiation factors; this stimulation was evident at 15 min and maximal by 60 min. These results suggest a potential general mechanism by which insulin could preferentially stimulate translation of mRNAs whose 5'UTRs exhibit significant secondary structure by activating initiation factors involved in melting such secondary structures.

Language of Publication

English

Unique Identifier

91115858

MeSH Heading (Major)

Insulin|*PD; Ornithine Decarboxylase|*BI/GE; Peptide Initiation Factors|*ME; RNA, Messenger|*CH/GE

MeSH Heading

Animal; Blotting, Northern; Cell Line; Cloning, Molecular; Cycloheximide|PD; Dactinomycin|PD; Dose-Response Relationship, Drug; Enzyme Induction; Human; Mice; Nucleic Acid Conformation; Phosphorylation; Receptors, Insulin|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Translation, Genetic

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (eIF-4B); 0 (eIF-4E); 0 (Peptide Initiation Factors); 0 (Receptors, Insulin); 0 (RNA, Messenger); 11061-68-0 (Insulin); 50-76-0 (Dactinomycin); 66-81-9 (Cycloheximide)

Record 20 from database: MEDLINE
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Title

Polyamine involvement in the growth of hormone-responsive and -resistant human breast cancer cells in culture.

Author

Glikman P; Manni A; Demers L; Bartholomew M

Address

Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

Source

Cancer Res, 1989 Mar 15, 49:6, 1371-6

Abstract

Recent evidence indicates that hormone-responsive but not -resistant human breast cancer cells in culture are sensitive to the antiproliferative effect of the polyamine (PA) biosynthetic inhibitor alpha-difluoromethylornithine (DFMO). The present experiments were designed to investigate the potential differential involvement of the PA pathway in the growth of these different biological subtypes of human breast cancer. Thus, we evaluated the effect of DFMO on proliferation, ornithine decarboxylase (ODC) activity, and PA levels of the hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. When tested at comparable cell density, the two cell lines had similar levels of ODC activity and PA. Administration of DFMO (0.01, 0.1, 1, 4 mM) for 6 days caused a similar dose-dependent inhibition of proliferation (up to approximately 15% of control) associated with suppression of ODC activity to undetectable levels at the highest dose. In both cell lines, putrescine and spermidine levels were maximally suppressed by doses of DFMO greater than 0.1 mM. Higher doses of DFMO (1 and 4 mM) also suppressed spermine levels to approximately 60% of control. In detailed time-course studies, DFMO administration (0.1 mM) similarly suppressed by 80% the rise in ODC observed in both cell lines following a medium change. At all time points, putrescine and spermidine levels were likewise suppressed to a similar extent. Addition of putrescine (0.1-2.5 mM) to DFMO-treated cells repleted cellular PA levels and restored growth to approximately 80% of control in both cell lines. We conclude that, under these experimental conditions, PA are similarly involved in the growth of the hormone-responsive MCF-7 and -resistant MDA-MB-231 human breast cancer cell lines.

Language of Publication

English

Unique Identifier

89168158

MeSH Heading (Major)

Biogenic Polyamines|*PH; Breast Neoplasms|*PA; Neoplasms, Hormone-Dependent|*PA

MeSH Heading

Cell Count; Dose-Response Relationship, Drug; Eflornithine|PD; Female; Human; Ornithine Decarboxylase|AN; Putrescine|PD; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0008-5472

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Biogenic Polyamines); 110-60-1 (Putrescine); 70052-12-9 (Eflornithine)

Record 21 from database: MEDLINE
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Title

Polyamine involvement in the secretion and action of TGF-alpha in hormone sensitive human breast cancer cells in culture.

Author

Kim I; Manni A; Lynch J; Demers L

Address

Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033.

Source

Breast Cancer Res Treat, 1991 May, 18:2, 83-91

Abstract

These experiments were designed to test polyamine (PA) involvement in the secretion and action of transforming growth factor alpha (TGF-alpha) in hormone responsive MCF-7 breast cancer cells in liquid culture. At the same time, we evaluated the influence of culture conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA involvement in estrogen (E2) and TGF-alpha stimulated cell proliferation. Despite inducing a profound suppression of cellular PA levels and inhibiting basal and E2-stimulated growth, administration of the PA synthesis inhibitor alpha-difluoromethylornithine (DFMO) did not influence either basal or E2-induced TGF-alpha secretion. In the same experiments, on the other hand, addition of DFMO completely blocked the growth stimulatory effect of exogenous TGF-alpha. However, when the culture conditions were changed to serum-free medium, TGF-alpha and E2-induced cell proliferation was affected modestly or not at all by DFMO administration, despite similar suppression of cellular ornithine decarboxylase (ODC) activity and PA levels. In addition, different clones of MCF-7 cells differed in their sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC activity and PA. We conclude that PAs are not involved in basal or E2-stimulated TGF-alpha secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important mediators of TGF-alpha and E2-induced breast cancer cell proliferation, though the degree of such involvement appears to be influenced by serum factors and clonal variability of MCF-7 cells.

Language of Publication

English

Unique Identifier

92004007

MeSH Heading (Major)

Breast Neoplasms|*ME/PA; Polyamines|*PD; Transforming Growth Factor alpha|*SE

MeSH Heading

Cell Division|DE; Eflornithine|PD; Estrogens|PH; Human; In Vitro; Neoplasms, Hormone-Dependent; Putrescine|PD/PH; Serum Albumin, Bovine|PD; Spermidine|PH; Spermine|PH; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Estrogens); 0 (Polyamines); 0 (Serum Albumin, Bovine); 0 (Transforming Growth Factor alpha); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 70052-12-9 (Eflornithine); 71-44-3 (Spermine)

Record 22 from database: MEDLINE
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Title

Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders.

Author

Lambert MI; Hefer JA; Millar RP; Macfarlane PW

Address

Dept. of Physiology, University of Cape Town Medical School, South Africa.

Source

Int J Sport Nutr, 1993 Sep, 3:3, 298-305

Abstract

Amino acids are commonly ingested as ergogenic acids in the belief that they enhance protein synthesis and stimulate growth hormone release. The aim of this study was to determine the acute effect that amino acid supplements have on serum growth hormone (GH) concentration. Seven male body-builders reported to the laboratory on four occasions after an 8-hr fast and ingested, in random order, either a placebo, a 2.4-g arginine/lysine supplement, a 1.85-g ornithine/tyrosine supplement, or a 20-g BovrilR drink. Blood was collected before each treatment and again every 30 minutes for 3 hours for the measurement of serum GH concentration. On a separate occasion, subjects had an intravenous infusion of 0.5 microgram GH-releasing hormone.kg-1 body weight to confirm that GH secretory response was normal. The main finding was that serum GH concentrations were not altered consistently in healthy young males following the ingestion of the amino acid supplements in the quantities recommended by the manufacturers.

Language of Publication

English

Unique Identifier

94035086

MeSH Heading (Major)

Amino Acids|AD/*PD; Somatotropin|AD/BL/*DE; Weight Lifting|*PH

MeSH Heading

Administration, Oral; Adult; Human; Male; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

1050-1606

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amino Acids); 9002-72-6 (Somatotropin)

Record 23 from database: MEDLINE
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Title

Cellular and molecular basis of intestinal and pancreatic adaptation.

Author

Dowling RH

Address

Gastroenterology Unit, Guy's Hospital, London, U.K.

Source

Scand J Gastroenterol Suppl, 1992, 193:, 64-7

Abstract

This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.

Language of Publication

English

Unique Identifier

93174201

MeSH Heading (Major)

Adaptation, Physiological|*; Intestines|ME/PA/*PH; Pancreas|ME/PA/*PH

MeSH Heading

Amine Oxidase (Copper-Containing)|ME; Animal; Cell Division; Human; Hyperplasia; Polyamines|ME; RNA, Messenger

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0085-5928

Country of Publication

NORWAY

CAS Registry/EC Number

EC 1.4.3.6 (Amine Oxidase (Copper-Containing)); 0 (Polyamines); 0 (RNA, Messenger)

Record 24 from database: MEDLINE
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Title

Effects of parathyroid hormone on ornithine decarboxylase activity in human osteosarcoma cells.

Author

Goto H; Matsui-Yuasa I; Otani S; Morisawa S; Nishizawa Y; Morii H

Address

Department of Biochemistry, Osaka City University Medical School, Japan.

Source

Arch Biochem Biophys, 1991 May 1, 286:2, 316-22

Abstract

Ornithine decarboxylase (ODC) is a rate-limiting enzyme of the biosynthesis of polyamines, which are important in cell growth and differentiation. Here, we studied whether parathyroid hormone (PTH) affects the induction of ODC and the proliferation of the human osteoblast-like cell line SaOS2, which is sensitive to PTH. In confluent cells, ODC activity was not detected, but activity was significantly induced by fresh medium, with maximum activity 6 h after the change. PTH potentiated this enzyme induction in a dose-dependent manner at 10(-9) and 10(-8) M at which range the intracellular cAMP level also rose. Dibutyryl cAMP, cholera toxin, and 3-isobutyl-1-methylxanthine each caused an increase in ODC activity similar to that with PTH. The half-life of enzyme activity was about 30 min and was not changed by the addition of PTH. mRNA coding for ODC was detected in the confluent cells and its concentration was increased two- to threefold by the fresh medium. No further increase in mRNA occurred when PTH was added. At 48 h after the change of medium, PTH inhibited the DNA synthesis induced by fresh medium. These results suggest that the increase in ODC activity caused by PTH was caused by enhancement of cAMP synthesis, and that this augmentation involves post-transcriptional regulation.

Language of Publication

English

Unique Identifier

91378318

MeSH Heading (Major)

Cyclic AMP|*ME; Ornithine Decarboxylase|*ME; Parathyroid Hormones|*PD; Peptide Fragments|*PD

MeSH Heading

Bucladesine|PD; Butyric Acids|PD; Cell Line; DNA Replication|DE; Eflornithine|PD; Human; Kinetics; Nucleic Acid Hybridization; Osteosarcoma; Polyamines|ME; RNA, Neoplasm|GE/IP

Publication Type

JOURNAL ARTICLE

ISSN

0003-9861

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Butyric Acids); 0 (Parathyroid Hormones); 0 (Peptide Fragments); 0 (Polyamines); 0 (RNA, Neoplasm); 107-92-6 (butyric acid); 362-74-3 (Bucladesine); 52232-67-4 (Teriparatide); 60-92-4 (Cyclic AMP); 70052-12-9 (Eflornithine)

Record 25 from database: MEDLINE
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Title

Variations in amplification and expression of the ornithine decarboxylase gene in human breast cancer cells.

Author

Thomas T; Kiang DT; Jänne OA; Thomas TJ

Address

Department of Environmental and Community Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.

Source

Breast Cancer Res Treat, 1991 Nov, 19:3, 257-67

Abstract

The polyamine biosynthetic pathway plays a critical role in the growth of human breast cancer cells. Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. To understand the regulation of ODC activity and polyamine accumulation in breast cancer cells, we studied amplification and expression of the ODC gene in four breast cancer cell lines. ODC gene dosage was analyzed by Southern blot hybridization and was 4- to 12-fold higher in T-47D, MDA-MB-231, and BT-20 cell lines than in the MCF-7 cell line. ODC mRNA level was 2- to 3-fold higher in BT-20 and MDA-MB-231 cell lines than in the other two lines. We also measured ODC activity and polyamine concentration in these cell lines, and determined their sensitivity to an ODC inhibitor, difluoromethylornithine (DFMO). BT-20 cells showed significantly higher ODC activity and polyamine concentrations than the other three cell lines. BT-20 cells were resistant to the growth inhibitory effect of DFMO even at 4 mM concentration, whereas the proliferation of MCF-7, T47D, and MDA-MB-231 cells was inhibited by this drug. These results suggest that different transcriptional and post-transcriptional mechanisms control the regulation of ODC gene expression in breast cancer cell lines.

Language of Publication

English

Unique Identifier

92135858

MeSH Heading (Major)

Adenocarcinoma|EN/*PA; Breast Neoplasms|EN/*PA; Carcinoma|EN/*PA; Carcinoma, Intraductal, Noninfiltrating|EN/*PA; Neoplasm Proteins|BI/*GE; Ornithine Decarboxylase|BI/*GE

MeSH Heading

Comparative Study; DNA, Neoplasm|GE; Eflornithine|PD; Enzyme Induction; Estrogens; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Human; Neoplasms, Hormone-Dependent|EN/PA; Polyamines|AN; RNA, Messenger|BI; RNA, Neoplasm|AN; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured|DE/EN

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (DNA, Neoplasm); 0 (Estrogens); 0 (Neoplasm Proteins); 0 (Polyamines); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 70052-12-9 (Eflornithine)

Record 26 from database: MEDLINE
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Title

Comparison of growth hormone response to growth hormone-releasing factor 1-44 according to the combined study of sleep secretion with the responses to pharmacologic stimuli.

Author

Garnier P; Liapi C; Raynaud F; Evain-Brion D

Address

Fondation de Recherche en Hormonologie, Fresnes, France.

Source

Horm Res, 1987, 28:1, 13-9

Abstract

The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22 females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients were also submitted to a standard evaluation of their GH secretion, consisting of at least two classical pharmacologic stimulation (CPS) tests, such as ornithine, arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n = 26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV) dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS. There was a large overlap of the individual responses to GRF between the 5 groups, but the mean responses in groups II, IV and V were significantly lower than in group I. Furthermore, the mean responses of groups IV and V were in the lower range of the normal. It is concluded that the GRF test may be useful to ascertain the diagnosis of functional or partial GH deficiency when the responses to CPS and SS are dissociated.

Language of Publication

English

Unique Identifier

88197053

MeSH Heading (Major)

Growth Disorders|*ME; Sleep|*PH; Somatotropin|DF/*SE; Somatotropin-Releasing Hormone|*DU

MeSH Heading

Adolescence; Adult; Child; Child, Preschool; Comparative Study; Female; Human; Male; Pituitary Function Tests|MT; Pituitary Gland|DE/SE

Publication Type

JOURNAL ARTICLE

ISSN

0301-0163

Country of Publication

SWITZERLAND

CAS Registry/EC Number

9002-72-6 (Somatotropin); 9034-39-3 (Somatotropin-Releasing Hormone)

Record 27 from database: MEDLINE
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Title

Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed weighting index.

Author

Rochiccioli P; Enjaume C; Tauber MT; Pienkowski C

Address

Service de Pédiatrie, CHU Purpan, Toulouse, France.

Source

Acta Paediatr, 1993 Mar, 82:3, 245-8

Abstract

A total of 5473 pharmacological stimulation tests were carried out in 3143 children and subjected to statistical analysis. The mean chronological age of the children was 9 years 9 months (range 3 years to 16 years 6 months) and mean bone age was 7 years 6 months (range 2 years to 14 years). Nine pharmacological tests were used: (1) arginine (n = 625); (2) clonidine (n = 339); (3) insulin (n = 198); (4) ornithine (n = 162); (5) insulin and arginine (n = 203); (6) clonidine and betaxolol (n = 2003); (7) L-dopa (n = 685); (8) glucagon and propranolol (n = 443); and (9) glucagon and betaxolol (n = 815). Measurement of plasma growth hormone was always performed using the same method. The distribution of values in each test was of the gausso-logarithmic type. The results of the mean peak and the 95% confidence limit were as follows: (1) 10.2, 0.45; (2) 11.5, 0.7; (3) 11.8, 0.8; (4) 14.2, 1.2; (5) 14.3, 0.9; (6) 15.7, 1.1; (7) 19.8, 2.1; (8) 20.8, 2.3; (9) 21, 2.5. These results lead to the following conclusions: the specificity of these tests is low, the mean peak may vary two-fold from one test to another, and the percentage of peaks < 10 ng/ml ranges from 69% for test 1 to 29% for tests 8 and 9. The proportion of growth hormone deficiencies thus varies considerably according to the test used.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

93264725

MeSH Heading (Major)

Drugs|*DU; Growth Disorders|BL/*DI

MeSH Heading

Adolescence; Child; Child, Preschool; Comparative Study; Female; Human; Male; Retrospective Studies; Sensitivity and Specificity; Somatotropin|BL/DF

Publication Type

JOURNAL ARTICLE

ISSN

0803-5253

Country of Publication

NORWAY

CAS Registry/EC Number

0 (Drugs); 9002-72-6 (Somatotropin)

Record 28 from database: MEDLINE
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Title

Human promyelocytic cell line HL60 has the specific binding sites for prolactin and its ornithine decarboxylase, DNA synthesis and cellular proliferation are induced by prolactin.

Author

Nishiguchi Y; Hibasami H; Komada Y; Sakurai M; Nakashima K

Address

Department of Biochemistry, Mie University Faculty of Medicine, Japan.

Source

Leuk Res, 1993 Aug, 17:8, 633-7

Abstract

Human prolactin (hPRL) induced ornithine decarboxylase (ODC) activity, subsequently DNA synthesis and cellular proliferation on human promyelocytic cells, HL60, cultured in a serum-free medium. HL60 cells had 2100 specific binding sites for hPRL per cell, showing a dissociation constant of 1.1 x 10(-10) M. Binding of 125I-PRL to the cells was not blocked by simultaneous addition of human growth hormone. ODC activity and DNA synthesis were activated maximally at 5 and 20 h, respectively, after the addition of 0.05 nM hPRL. These effects of PRL on cellular proliferation, ODC activity and DNA synthesis were abolished by the simultaneous addition of anti-hPRL antibody. Simultaneous addition of an irreversible inhibitor of ODC, difluoromethyl ornithine (DFMO), also abolished the inductions of ODC and DNA synthesis by hPRL. The inhibitory effect of DFMO on hPRL-induced DNA synthesis was reversed by the addition of putrescine to the culture medium. These results suggest that hPRL binds to the prolactin receptor on HL60 cells and induces ODC activity to increase cellular polyamine levels, which eventually stimulates DNA synthesis and cellular proliferation.

Language of Publication

English

Unique Identifier

93360545

MeSH Heading (Major)

Cell Division|*DE; DNA Replication|*DE; Leukemia, Promyelocytic, Acute|*ME/PA; Ornithine Decarboxylase|*BI; Prolactin|ME/*PD; Receptors, Prolactin|*BI

MeSH Heading

Binding Sites; Carbon Radioisotopes; Dose-Response Relationship, Drug; DNA, Neoplasm|BI; Enzyme Induction; Human; Iodine Radioisotopes; Kinetics; Thymidine|ME; Tritium; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0145-2126

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Carbon Radioisotopes); 0 (DNA, Neoplasm); 0 (Iodine Radioisotopes); 0 (Receptors, Prolactin); 10028-17-8 (Tritium); 50-89-5 (Thymidine); 9002-62-4 (Prolactin)

Record 29 from database: MEDLINE
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Title

Retinoic acid regulates ornithine decarboxylase gene expression at the transcriptional level.

Author

Mao Y; Gurr JA; Hickok NJ

Address

Department of Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107.

Source

Biochem J, 1993 Nov 1, 295 ( Pt 3):, 641-4

Abstract

Retinoic acid (RA) is important for normal mammalian development and growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the biosynthesis of the polyamines, and we have previously shown that ODC mRNA levels are suppressed by RA in human skin cells. Using HeLa cells, we now show that treatment with 0.5 microM RA for 24 h suppresses endogenous ODC mRNA levels and the expression of a transfected ODC/chloramphenicol acetyltransferase plasmid (Kpn-ODCCAT), containing sequences from -1450 to +810 of the human ODC gene. Co-transfection with either the alpha-RA receptor (alpha-RAR) or a chimeric alpha-RA/oestrogen receptor (alpha-RAER) followed by treatment with the cognate hormone suppresses expression of Kpn-ODCCAT and Not-ODCCAT, which contains sequences from -250 to +514. Liganded alpha-RAR suppresses the activity of Kpn-ODCCAT more markedly than does liganded alpha-RAER (98% and 80% suppression, respectively), whereas both receptors have very similar effects on Not-ODCCAT expression (73% and 67% suppression, respectively). The unliganded alpha-RAR suppresses Kpn-ODCCAT by 76%, whereas unliganded alpha-RAER has no significant effect. These data show that RA regulates ODC-gene expression at the transcriptional level, and that alpha-RAR, but not alpha-RAER, can confer full hormonal responsiveness. This suggests that the activating function present in the alpha-RAR ligand-binding domain is required for full transcriptional regulation.

Language of Publication

English

Unique Identifier

94059011

MeSH Heading (Major)

Gene Expression Regulation|*DE; Ornithine Decarboxylase|*GE; Transcription, Genetic|*DE; Tretinoin|*PD

MeSH Heading

Animal; Blotting, Northern; Cell Line; Cercopithecus aethiops; Hela Cells; Human; Kidney; Receptors, Estrogen|GE/PH; Receptors, Retinoic Acid|GE/PH; RNA, Messenger|ME; Support, U.S. Gov't, P.H.S.; Transfection

Publication Type

JOURNAL ARTICLE

ISSN

0264-6021

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Estrogen); 0 (Receptors, Retinoic Acid); 0 (RNA, Messenger); 302-79-4 (Tretinoin)

Record 30 from database: MEDLINE
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Title

Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters.

Author

Fogelholm GM; Näveri HK; Kiilavuori KT; Härkönen MH

Address

Dept. of Applied Chemistry and Microbiology, University of Helsinki, Finland.

Source

Int J Sport Nutr, 1993 Sep, 3:3, 290-7

Abstract

Using a double-blind, crossover protocol, we studied the possible effects of a 4-day combined L-arginine, L-ornithine, and L-lysine supplementation (each 2 g/day, divided into two daily doses) on 24-hr level of serum human growth hormone (hGH) and insulin in 11 competitive weightlifters, ages 19 to 35 yrs. Three similar daily hGH peaks, seemingly preceded by a decrease in serum insulin concentration, were found during both amino acid and placebo supplementation. Supplementation did not affect the physiological variation of serum hGH concentration (treatment and treatment x time interaction: p = 0.43-0.55). Analogously, serum insulin levels were not higher after amino acid supplementation. Therefore the ergogenic value of low-dose oral amino acid supplementation in increasing hGH or insulin secretion seems questionable.

Language of Publication

English

Unique Identifier

94035085

MeSH Heading (Major)

Amino Acids|AD/*PD; Somatotropin|BL/*DE; Weight Lifting|*PH

MeSH Heading

Adult; Double-Blind Method; Drug Administration Schedule; Human; Insulin|ME; Male; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

1050-1606

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amino Acids); 11061-68-0 (Insulin); 9002-72-6 (Somatotropin)

Record 31 from database: MEDLINE
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Title

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

Author

Janáky T; Juhász A; Bajusz S; Csernus V; Srkalovic G; Bokser L; Milovanovic S; Redding TW; Rékási Z; Nagy A; et al

Address

Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA.

Source

Proc Natl Acad Sci U S A, 1992 Feb 1, 89:3, 972-6

Abstract

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3, Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D- Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models.

Language of Publication

English

Unique Identifier

92141240

MeSH Heading (Major)

Cytotoxins|*AD; Gonadorelin|*AA/ME; Hormones, Synthetic|*CH

MeSH Heading

Amino Acid Sequence; Animal; Antimetabolites, Antineoplastic|AD; Cell Division|DE; Human; In Vitro; Molecular Sequence Data; Rats; Receptors, LHRH|ME; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Antimetabolites, Antineoplastic); 0 (Cytotoxins); 0 (Hormones, Synthetic); 0 (Receptors, LHRH); 33515-09-2 (Gonadorelin)

Record 32 from database: MEDLINE
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Title

Role of gastrin as a trophic hormone.

Author

Walsh JH

Address

Center for Ulcer Research and Education, Wadsworth Veterans Administration Center, Los Angeles, Calif.

Source

Digestion, 1990, 47 Suppl 1:, 11-6; discussion 49-52

Abstract

Gastrin has two principal biological effects: stimulation of acid secretion from gastric parietal cells and stimulation of mucosal growth in the acid-secreting part of the stomach. Circulating gastrin regulates the increase in acid secretion that occurs during the after meals. Gastrin also stimulates mucosal growth in the stomach. Exogenously administered gastrin causes increased cell division in the proliferative zone that lies between the surface cells and the gastric glands in the acid-secreting mucosa. The newly formed cells undergo differentiation into surface epithelial cells, parietal cells and gastric enterochromaffin-like cells. Furthermore, the increased mucosal proliferation that occurs with refeeding after a period of fasting may be mediated by gastrin since refeeding stimulates gastrin production and a parallel increase in mucosal DNA synthesis. Both food and gastrin cause a rapid increase in cell division and an increase in gastric ornithine decarboxylase mRNA in fasting rats. In preliminary immunoneutralization experiments, the stimulation of ornithine decarboxylase produced by food was inhibited by gastrin antibody. The sustained inhibition of gastric acid secretion obtained by surgery or with antisecretory drug therapy results in hypergastrinaemia associated with increased gastric mucosal cell proliferation. A good correlation between gastric enterochromaffin-like cell density and circulating gastrin concentrations has been found under these conditions as well as during infusions of exogenous gastrin. Trophic effects of gastrin have also been reported for the colon, duodenum and pancreas, but chronic hypergastrinaemia does not appear to produce hyperplasia of these organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

91231139

MeSH Heading (Major)

Gastric Acid|*SE; Gastrins|PD/*PH; Parietal Cells, Gastric|*SE

MeSH Heading

Animal; Cell Division|DE; Gastric Mucosa|CY/DE; Human; Omeprazole|PD

Publication Type